The objectives in this research program are to develop new methods for the quantitative determination and for the speciation of trace (ppm to ppb) elements in complex solid or liquid matrices. Elemental profiles in environmental and biological samples have been obtained by X-ray fluorescence (XRF) and at trace levels, by proton induced X-ray emission (PIXE). This analytical capability will be developed further with special attention being devoted to improving techniques of sample preparation. This multielemental technique will be used for the speciation of heavy elements. This will be accomplished by carrying out preconcentration and chemical separations of the various species, for example, the four arsenic species commonly encountered in biological samples, and employing the PIXE technique for determining the elemental concentration. Alternative methods based on the kinetic control of chemical reactions will be explored for the speciation of elements such as arsenic. The most important objective in this research program is to extend the PIXE capability to include the use of a proton microprobe (micro-PIXE) for the measurement of elemental concentrations in microscopic size samples. Elemental profiles will be determined in a target area 100 mum x 100 mum, by rastering a 1 mum x 1 mum proton beam across this target area. Precautions will be taken to minimize sample degradation by the effects of heat and radiation damage. Elemental maps of tissue slices and single cells will be obtained with this micro-PIXE system.